The long term objective of this study is to develop a non-invasive, non- radioactive breath test for determining cytochrome P450 3A4 (CYP3A4) activity. This enzyme accounts for one-third of the total cytochromes present in adult human liver and the majority present in human small bowel. Approximately one-third of the new drugs under development are substrates whose rate of metabolism is predominately determined by CYP3A4. This test will be a valuable tool for identifying in vivo inducers and inhibitors of this enzyme and predicting important drug interactions. Furthermore, this test can be used to predict the bioavailability of CYP3A4 substrates to determine safe therapeutic ranges and individual patient dosing. The experiments in Phase II will demonstrate the reliability, accuracy and safety of the breath test to obtain FDA clearance. The test is unique as a non-invasive, non-radioactive probe to selectively determine CYP3A4 liver and intestinal activity in vivo. It has enormous commercial application because the information will shorten the drug development cycle. In addition, the test provides information critical to predicting and avoiding adverse drug.reactions. PROPOSED COMMERCIAL APPLICATION: The proposed test will be an accurate, low cost and FDA approved method for selectively determining liver and intestinal CYP3A4 activity. The market will be pharmaceutical companies to streamline the drug development cycle, predict proper dosing of drugs with a narrow therapeutic index with little or no blood level monitoring, and make commercially viable many drugs that are abandoned due to lack of ways to properly dose them.